Stefano Rivetti

Physical and psychophysical characterization of a novel clinical system for digital mammography

PURPOSE In recent years, many approaches have been investigated on the development of full-field digital mammography detectors and implemented in practical clinical systems. Some of the most promising techniques are based on flat panel detectors, which, depending on the mechanism involved in the x-ray detection, can be grouped into direct and indirect flat panels. Direct detectors display a better spatial resolution due to the direct conversion of x rays into electron-hole pairs, which do not need an intermediate production of visible light. In these detectors the readout is usually achieved through arrays of thin film transistors (TFTs). However, TFT readout tends to display noise characteristics worse than those from indirect detectors. To address this problem, a novel clinical system for digital mammography has been recently marketed based on direct-conversion detector and optical readout. This unit, named AMULET and manufactured by FUJIFILM, is based on a dual layer of amorphous selenium that acts both as a converter of x rays (first layer) and as an optical switch for the readout of signals (second layer) powered by a line light source. The optical readout is expected to improve the noise characteristics of the detector. The aim is to obtain images with high resolution and low noise, thanks to the combination of optical switching technology and direct conversion with amorphous selenium. In this article, the authors present a characterization of an AMULET system. METHODS The characterization was achieved in terms of physical figures as modulation transfer function (MTF), noise power spectra (NPS), detective quantum efficiency (DQE), and contrast-detail analysis. The clinical unit was tested by exposing it to two different beams: 28 kV Mo/Mo (namely, RQA-M2) and 28 kV W/Rh (namely, W/Rh). RESULTS MTF values of the system are slightly worse than those recorded from other direct-conversion flat panels but still within the range of those from indirect flat panels: The MTF values of the AMULET system are about 45% and 15% at 5 and 8 lp/mm, respectively. On the other hand, however, AMULET NNPS results are consistently better than those from direct-conversion flat panels (up to two to three times lower) and flat panels based on scintillation phosphors. DQE results lie around 70% when RQA-M2 beams are used and approaches 80% in the case of W/Rh beams. Contrast-detail analysis, when performed by human observers on the AMULET system, results in values better than those published for other full-field digital mammography systems. CONCLUSIONS The novel clinical unit based on direct-conversion detector and optical reading presents great results in terms of both physical and psychophysical characterizations. The good spatial resolution, combined with excellent noise properties, allows the achievement of very good DQE, better than those published for clinical FFDM systems. The psychophysical analysis confirms the excellent behavior of the AMULET unit.

Comparison of different computed radiography systems: Physical characterization and contrast detail analysis

PURPOSE In this study, five different units based on three different technologies-traditional computed radiography (CR) units with granular phosphor and single-side reading, granular phosphor and dual-side reading, and columnar phosphor and line-scanning reading-are compared in terms of physical characterization and contrast detail analysis. METHODS The physical characterization of the five systems was obtained with the standard beam condition RQA5. Three of the units have been developed by FUJIFILM (FCR ST-VI, FCR ST-BD, and FCR Velocity U), one by Kodak (Direct View CR 975), and one by Agfa (DX-S). The quantitative comparison is based on the calculation of the modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE). Noise investigation was also achieved by using a relative standard deviation analysis. Psychophysical characterization is assessed by performing a contrast detail analysis with an automatic reading of CDRAD images. RESULTS The most advanced units based on columnar phosphors provide MTF values in line or better than those from conventional CR systems. The greater thickness of the columnar phosphor improves the efficiency, allowing for enhanced noise properties. In fact, NPS values for standard CR systems are remarkably higher for all the investigated exposures and especially for frequencies up to 3.5 lp/mm. As a consequence, DQE values for the three units based on columnar phosphors and line-scanning reading, or granular phosphor and dual-side reading, are neatly better than those from conventional CR systems. Actually, DQE values of about 40% are easily achievable for all the investigated exposures. CONCLUSIONS This study suggests that systems based on the dual-side reading or line-scanning reading with columnar phosphors provide a remarkable improvement when compared to conventional CR units and yield results in line with those obtained from most digital detectors for radiography.

A comparison of digital radiography systems in terms of effective detective quantum efficiency

PURPOSE The purpose of this study is to compare digital radiography systems using the metric effective detective quantum efficiency (eDQE), which better reflects digital radiography imaging system performance under clinical operating conditions, in comparison with conventional metrics such as modulation transfer function (MTF), normalized noise power spectra (NNPS), and detective quantum efficiency (DQE). METHODS The eDQE was computed by the calculation of the MTF, the NNPS, the phantom attenuation and scatter, and estimation of x-ray flux. The physical characterization of the systems was obtained with the standard beam conditions RQA5 and RQA9, using the PA Chest phantom proposed by AAPM Report # 31 simulating the attenuation and scatter characteristics of the adult human thorax. The MTF (eMTF) was measured by using an edge test placed at the frontal surface of the phantom, the NNPS (eNNPS) was calculated from images of the phantom acquired at three different exposure levels covering the operating range of the system (E(0), which is the exposure at which a system is normally operated, 1/3 E(0), and 3 E0), and scatter measurements were assessed by using a beam-stop technique. The integral of DQE (IDQE) and eDQE (IeDQE) was calculated over the whole spatial frequency range. RESULTS The eMTF results demonstrate degradation due to magnification and the presence of scattered radiation. The eNNPS was influenced by the grid presence, and in some systems, it contained structured noise. At typical clinical exposure levels, the magnitude of eDQE(0) with respect to DQE(0) at RQA9 beam conditions was 13%, 17%, 16%, 36%, and 24%, respectively, for Carestream DRX-1, Carestream DRX-1C, Carestream Direct View CR975, Philips Digital Diagnost VM, and GE Revolution XR/d. These results were confirmed by the ratio of IeDQE and IDQE in the same conditions. CONCLUSIONS The authors confirm the robustness and reproducibility of the eDQE method. As expected, the DR systems performed better than the CR systems due to their superior signal-to-noise transfer characteristics. The results of this study suggest the eDQE method may provide an opportunity to more accurately assess the clinical performance of digital radiographic imaging systems by accounting for factors such as the presence of scatter, use of an antiscatter grid, and magnification and focal spot blurring effects, which are not reflected in conventional DQE measures.

A role for epidermal growth factor receptor in idiopathic pulmonary fibrosis onset

In idiopathic pulmonary fibrosis (IPF) patients the presence of missense polymorphisms (SNP) in members of the epidermal growth factor receptor (EGFR) family or their genetic association could influence the binding affinity of natural ligands, modifying the expression and the behavior of the correlated genes. EGFR family members are particularly involved in the epithelial injury and fibrotic process in IPF. Genetic variations in HER family of receptors may alter the possible therapeutic efficacy of EGFR inhibitors. This study aimed to analyze the relationships between IPF and specific EGF receptor family functional polymorphisms. We tested the presence of common EGFR, HER2 and HER3 non-synonymous SNPs in the peripheral blood of 20 Italian IPF patients and their association with the disease. Our data indicated that the HER2 variant allele frequency was significantly lower in patients than in controls, with an odds ratio of 0.31 (95% CI 0.080, 0.98). Our finding suggests that HER2 variant could be a protective factor against IPF onset.

Free software for performing physical analysis of systems for digital radiography and mammography

PURPOSE In this paper, the authors present a free software for assisting users in achieving the physical characterization of x-ray digital systems and image quality checks. METHODS The program was developed as a plugin of a well-known public-domain suite ImageJ. The software can assist users in calculating various physical parameters such as the response curve (also termed signal transfer property), modulation transfer function (MTF), noise power spectra (NPS), and detective quantum efficiency (DQE). It also includes the computation of some image quality checks: defective pixel analysis, uniformity, dark analysis, and lag. RESULTS The software was made available in 2009 and has been used during the last couple of years by many users who gave us valuable feedback for improving its usability. It was tested for achieving the physical characterization of several clinical systems for digital radiography and mammography. Various published papers made use of the outcomes of the plugin. CONCLUSIONS This software is potentially beneficial to a variety of users: physicists working in hospitals, staff working in radiological departments, such as medical physicists, physicians, engineers. The plugin, together with a brief user manual, are freely available and can be found online (www.medphys.it/downloads.htm). With our plugin users can estimate all three most important parameters used for physical characterization (MTF, NPS, and also DQE). The plugin can run on any operating system equipped with ImageJ suite. The authors validated the software by comparing MTF and NPS curves on a common set of images with those obtained with other dedicated programs, achieving a very good agreement.

A new clinical unit for digital radiography based on a thick amorphous Selenium plate: Physical and psychophysical characterization

PURPOSE Here, we present a physical and psychophysical characterization of a new clinical unit (named AcSelerate) for digital radiography based on a thick a-Se layer. We also compared images acquired with and without a software filter (named CRF) developed for reducing sharpness and noise of the images and making them similar to images coming from traditional computed radiography systems. METHODS The characterization was achieved in terms of physical figures of merit [modulation transfer function (MTF), noise power spectra (NPS), detective quantum efficiency (DQE)], and psychophysical parameters (contrast-detail analysis with an automatic reading of CDRAD images). We accomplished measurements with four standard beam conditions: RAQ3, RQA5, RQA7, and RQA9. RESULTS The system shows an excellent MTF (about 50% at the Nyquist frequency). The DQE is about 55% at 0.5 lp/mm and above 20% at the Nyquist frequency and is almost independent from exposure. The contrast-detail curves are comparable to some of the best published data for other systems devoted to imaging in general radiography. The CRF filter influences both the MTF and NPS, but it does lead to very small changes on DQE. Also the visibility of CDRAD details is basically unaltered, when the filter is activated. CONCLUSIONS As normally happens with detector based on direct conversion, the system presents an excellent MTF. The improved efficiency caused by the thick layer allows getting good noise characteristics and DQE results better (about 10% on average) than many of the computed radiography (CR) systems and comparable to those obtained by the best systems for digital radiography available on the market.

Characterization of a clinical unit for digital radiography based on irradiation side sampling technology

PURPOSE A characterization of a clinical unit for digital radiography (FUJIFILM FDR D-EVO) is presented. This system is based on the irradiation side sampling (ISS) technology and can be equipped with two different scintillators: one traditional gadolinium-oxysulphide phosphor (GOS) and a needle structured cesium iodide (CsI) phosphor panel. METHODS The characterization was achieved in terms of response curve, modulation transfer function (MTF), noise power spectra (NPS), detective quantum efficiency (DQE), and psychophysical parameters (contrast-detail analysis with an automatic reading of CDRAD images). For both scintillation screens the authors accomplished the measurements with four standard beam conditions: RAQ3, RQA5, RQA7, and RQA9. RESULTS At the Nyquist frequency (3.33 lp/mm) the MTF is about 35% and 25% for CsI and GOS detectors, respectively. The CsI scintillator has better noise properties than the GOS screen in almost all the conditions. This is particularly true for low-energy beams, where the noise for the GOS system can go up to a factor 2 greater than that found for CsI. The DQE of the CsI detector reaches a peak of 60%, 60%, 58%, and 50% for the RQA3, RQA5, RQA7, and RQA9 beams, respectively, whereas for the GOS screen the maximum DQE is 40%, 44%, 44%, and 35%. The contrast-detail analysis confirms that in the majority of cases the CsI scintillator is able to provide improved outcomes to those obtained with the GOS screen. CONCLUSIONS The limited diffusion of light produced by the ISS reading makes possible the achievement of very good spatial resolution. In fact, the MTF of the unit with the CsI panel is only slightly lower to that achieved with direct conversion detectors. The combination of very good spatial resolution, together with the good noise properties reached with the CsI screen, allows achieving DQE on average about 1.5 times greater than that obtained with GOS. In fact, the DQE of unit equipped with CsI is comparable to the best alternative methods available which are based on the same technology, and similar to others based on an a-Se direct conversion detectors.

Physical and psychophysical characterization of a GE senographe DS clinical system

Indirect-conversion FFDM systems usually present a lower spatial resolution, with respect to the direct-conversion one. This can put serious issues in mammography, since high resolution is required. Digital software has been developed for restoring the losses in spatial resolution caused by blurring in the scintillation phosphor. GE Senographe DS system gives users the possibility of using such restoration. Basically, a filtering can be performed on the acquired images, by activating the FineView software option. In this work we present a complete characterization of a clinical system, in terms of MTF, NPS, DQE, and contrast-detail analysis. Figures of merit have been calculated on images acquired with and without the FineView software. The effects of the restoration software are investigated, both on image quality parameters, and on contrast-detail visibility. The MTF of the FFDM system is improved when FineView is activated. On the other hand, NPS presents noticeably changes, especially at high frequencies. DQE is fairly independent from the exposure, when FineView filter is not activated, whereas it presents a clear spread over the exposures, when FineView is activated. CDMAM analysis does not show significant differences between images with or without the restoration filter. Besides, the Mo/Mo beam seems to provide slightly better results than the Rh/Rh one.

Gene expression profile of human colon cancer cells treated with cross-reacting material 197, a diphtheria toxin non-toxic mutant.

Cross-Reacting Material 197 (CRM197) is a diphtheria toxin non-toxic mutant that has shown antitumor activity in mice and humans. It is still unclear whether this anti-tumorigenic effect depends on its strong inflammatory-immunological property, its ability to inhibit heparin-binding epidermal growth factor (HB-EGF), or even its possible weak toxicity. CRM197 is utilized as a specific inhibitor of HB-EGF that competes for the epidermal growth factor receptor (EGFR), overexpressed in colorectal cancer and implicated in its progression. In this study we evaluate the effects of CRM197 on HT-29 human colon cancer cell line behaviour and, for CRM197 recognized ability to inhibit HB-EGF, its possible influence on EGFR activation. In particular, while HT-29 does not show any reduction of viability after CRM197 treatment (MTT modified assay), or changes in cell cycle distribution (flow cytometry), in EGFR localization, phospho-EGFR detected signals (immunohistochemistry) or in morphology (scanning electron microscopy, SEM) they show a change in the gene expression profile by microarray analysis (cDNA microarray SS-H19k8). The overexpression of genes like protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA), guanine nucleotide-binding protein G subunit alpha-1(GNAIl) and butyrophilin, subfamily 2, member A1 (BTN2A1) has been confirmed with real-time-qPCR. This is the first study where the CRM197 treatment on HT-29 shows a possible scarce implication of endogenous HB-EGF on EGFR expression and cancer cell development. At the same time, our results show the alteration of a specific and selected number of genes.

The EGFR R521K polymorphism influences the risk to develop colorectal cancer.

Epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been extensively investigated for its possible involvement in cancer development and progression. In colorectal cancer (CRC) EGFR family has been found frequently over-expressed, thus therapy targeting EGFR has been developed. Interestingly, it has been observed that genetic variants in these receptors may alter the therapeutic efficacy of EGFR inhibitors. Polymorphic variants in members of the EGFR family could influence different biologic activities, such as ligands affinity, dimerization efficiency, kinase activity, expression levels, with a consequent impact in signalling pathways and cell behaviour. This study aimed to verify whether single nucleotide polymorphisms (SNPs) of EGFR family members could represent susceptibility factors able to influence the risk to develop CRC. Peripheral blood of 70 Italian colon cancer patients and 72 healthy controls was used as a source of genomic DNA to investigate EGFR, HER2 and HER3 common non-synonymous SNPs. Genetic association tests were performed to verify a possible relationship with CRC. Evidence of genotype association was found for the R521K EGFR polymorphism under a dominant mode of inheritance (Mid-P=0.031). Genotypes with the variant allele of EGFR R521K SNP confer a risk reduction to develop CRC.